Structure determination of peptide-heme complexes / by M. Res B. Tech Nishit Goradia

Heme has been traditionally viewed as a stable protein cofactor in hemoproteins. Only recently it is also being viewed as a signaling and regulatory molecule that binds temporarily to proteins and regulates their activation or inhibition. Information on the structural characteristics of heme regulatory motifs (HRMs) is scarce. Based on known HRMs from literature, nona-peptides containing the three heme-iron coordinating amino acids cysteine, histidine and tyrosine were employed for structural characterization by NMR and other biophysical techniques. Diamagnetic gallium protoporphyrin IX was used as a substitute for paramagnetic heme in NMR spectroscopy. Among the known cysteine-based HRMs, the Cys-Pro containing peptides are well structured as compared to the His and Tyr-based peptides. Furthermore, the distance between two heme-iron coordinating amino acids in a protein plays a critical role in the formation of penta- or hexacoordination. The observations of the peptide studies were further investigated at the protein level. As one example, the heme regulation of the voltage-gated potassium channel Kv1.4 has been studied at the structural level. These channels are involved in the control of neuronal excitability and regulation of neurotransmitter release. The N-terminal stretch of this channel opens and closes (inactivation) in response to the current flow and thus shapes the action potential. Heme binds to this N-terminal stretch through a CXXH motif and a distant histidine, reversibly inhibits the inactivation and thus might play an important role of counteracting the effects associated with neuropathological conditions. This interaction has been investigated using NMR spectroscopy and a model for inhibition of channel inactivation has been proposed. Finally, our peptide-based structure investigation has paved way for the identification of several yet unknown heme-regulated proteins.

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Person: Goradia, Nishit [Author]
Corporate Author: Friedrich-Schiller-Universität Jena [Degree granting institution]
Format: Book
Language(s):English
Publication:Jena, [2016]
Printing place:Jena
Dissertation Note:Dissertation, Friedrich-Schiller-Universität Jena, 2016
Subjects:Cofaktor > Peptide > Strukturanalyse
Type of content:Hochschulschrift
Related resources:Erscheint auch als Online-Ausgabe: Structure determination of peptide-heme complexes
Notes:Kumulative Dissertation, enthält Beiträge aus verschiedenen Zeitschriften
Physical description:x, 221 Seiten : Illustrationen, Diagramme ; 30 cm
Basic Classification: 35.76 Aminosäuren, Peptide, Eiweiße
Further information:Inhaltsverzeichnis